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Osteopontin-Targeted and PPARδ-Agonist-Loaded Nanoparticles Efficiently Reduce Atherosclerosis in Apolipoprotein E(–/–) Mice

[Image: see text] Atherosclerosis is the leading cause of vascular pathologies and acute cardiovascular events worldwide. Early theranostics of atherosclerotic plaque formation is critical for the prevention of associated cardiovascular complications. Osteopontin (OPN) expression in vascular smooth...

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Detalles Bibliográficos
Autores principales: Huang, Xu, Zhang, Yang, Zhang, Weiwei, Qin, Cheng, Zhu, Yan, Fang, Yan, Wang, Yabin, Tang, Chengchun, Cao, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404512/
https://www.ncbi.nlm.nih.gov/pubmed/36033674
http://dx.doi.org/10.1021/acsomega.2c00575
Descripción
Sumario:[Image: see text] Atherosclerosis is the leading cause of vascular pathologies and acute cardiovascular events worldwide. Early theranostics of atherosclerotic plaque formation is critical for the prevention of associated cardiovascular complications. Osteopontin (OPN) expression in vascular smooth muscle cells (VSMCs) has been reported as a promising molecular target for the diagnosis and treatment of atherosclerotic plaques. The PPARδ agonist GW1516 has been shown to inhibit VSMC migration and apoptosis. However, GW1516 has low aqueous solubility and poor oral bioavailability, which are major obstacles to its broad development and application. In this study, GW1516@NP-OPN, which is anti-OPN-targeted and loaded with the PPARδ agonist GW1516, was synthesized using a nanoprecipitation method. The uptake of GW1516@NP-OPN was examined using fluorescence microscopy and flow cytometry assay in VSMC in vitro models. Using the Transwell assay and acridine orange/ethidium bromide staining methods, we observed that the inhibition of VSMCS migration and apoptosis was significantly higher in cells treated with GW1516@NP-OPN than those treated with free GW1516. The western blot assay further confirmed that GW1516@NP-OPN can increase FAK phosphorylation and TGF-βprotein expression. The effect of NPs was further tested in vivo. The atherosclerotic lesion areas were greatly decreased by GW1516@NP-OPN compared with the free drug treatment in apolipoprotein E(–/–) mice models. Consequently, our results showed that GW1516@NP-OPN stabilizes the PPARδ agonist aqueous formulation, improves its anti-plaque formation activities in vivo and in vitro, and can therefore be recommended for further development as a potential anti-atherosclerotic nanotherapy.